Status:

RECRUITING

Clinical Trial of AMG510 in Stage III Unresectable NSCLC KRAS p.G12C Patients and Ineligible for Chemo-radiotherapy

Lead Sponsor:

Fundación GECP

Conditions:

Non-small Cell Lung Cancer Stage III

KRAS P.G12C

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

Open-label, non-randomised, exploratory, phase II, multi-centre clinical trial. 43 unresectable stage III (IIIA-N2, IIIB, IIIC) KRAS p.G12C non-small cell lung cancer patients will be enrolled in this...

Detailed Description

This is an open-label, non-randomized, exploratory, phase II multi-centre clinical trial.The total sample size is 43 patients. The population to be included are unresectable stage III (IIIA-N2, IIIB, ...

Eligibility Criteria

Inclusion

  • 1\. Male or female, aged ≤ 80 years old
  • 2\. ECOG performance status of 0-1
  • 3\. Histologically or cytologically confirmed, unresectable Stage III (IIIA-N2, IIIB and IIIC) NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology.
  • 4\. Patients who have documentation of KRAS p.G12C prior to enrollment. This determination can be done either by solid or liquid biopsy.
  • 5\. No prior treatment for unresectable Stage III (IIIA-N2, IIIB and IIIC) NSCLC.
  • 6\. Having a life expectancy ≥ 12 weeks
  • 7\. Patients must be ineligible for concurrent chemo-radiotherapy because of:
  • Tumor size ≥ 5 cm and lymph node N2 involvement
  • The target lesion has to be bulky disease and/or more than 35% of the total volume of the two lungs should receive more than 20 Gy (V20) or inadequate pulmonary function
  • Interstitial Lung diseases
  • Prior treatment with thoracic radiotherapy for any reason
  • Or under decision of a tumor committee as inappropriate due to local characteristics to perform treatment upfront
  • 8\. PET-CT at baseline is mandatory to confirm the absence of distant disease and to confirm unresectable disease
  • 9\. PET-CT positive mediastinic adenopathies must be histologically confirmed. Mediastinic involvement could be considered without histological test when no margin can be distinguished in the lymph node mass.
  • 10\. Brain CT or MRI is mandatory
  • 11\. Patients with at least 1 measurable lesion, as defined by RECIST v1.1.
  • 12\. Adequate hematologic and organ function.
  • 13\. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
  • 14\. Willingness and ability to comply with scheduled visits and study procedures
  • 15\. For female patients of childbearing potential, a negative pregnancy test must have been documented prior to enrollment (within 14 days prior to enrollment).
  • 16\. For female patients of childbearing potential, agreement (by patient and/or partner) to usea highly effective form(s) of contraception that results in a low failure rate (\< 1% per year)when used consistently and correctly, and to continue its use for 7 days after the last dose of AMG510 (Sotorasib). No hormonal methods and preferably barrier method always containing a spermicide, intrauterine device (IUD): intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
  • 17\. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate \[\< 1% per year\] when used consistently and correctly, and to continue its use for 7 days after the last dose of AMG510 (Sotorasib).
  • 18\. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to enrollment.
  • 19\. QTc interval must be ≤ 470 msec in females and ≤ 450 msec in males, based on the average obtained from three ECG.

Exclusion

  • 1\. Patients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, ALK translocations or ROS1 mutations
  • 2\. Weight loss \>10% within the previous 3 months
  • 3\. Patients with uncontrolled neuropathy (sensory) grade 2 or greater regardless of cause according to CTCAE v5.0
  • 4\. Major surgery within 28 days of study day 1
  • 5\. Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication
  • 6\. Significant cardiovascular disease, such as New York Heart Association cardiac disease (ClassII or greater), myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina
  • 7\. Ongoing cardiac dysrhythmias of CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade or QTcF interval \> 470ms
  • 8\. Severe infections within 4 weeks prior to randomization including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia
  • 9\. Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization
  • 10\. Patients with any concomitant and uncontrolled medical disorder
  • 11\. Patients with vena cava syndrome
  • 12\. Malignant pleural or pericardial effusion: both will be considered as suggestive of metastaticdisease. Also, are excluded those with negative cytology but being exudates. Patients with non-visible by thoracic X-ray pleural effusion or too small to be safely punctured could be included.
  • 13\. Prior treatment with anti-neoplasic drugs
  • 14\. Malignancies other than NSCLC within 3 years prior to enrollment
  • 15\. Women who are pregnant, lactating, or intending to become pregnant during the study.
  • 16\. Positive test for HIV. All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the clinical study.
  • 17\. Patients with active hepatitis B or hepatitis C.
  • 18\. Active tuberculosis.
  • 19\. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
  • 20\. Patients with illnesses or conditions that interfere with their capacity to understand follow and/or comply with study procedures.
  • 21\. Known or suspected hypersensitivity to drugs with similar chemical structures to the study drug
  • 22\. Evidence of any other disorder or significant laboratory finding that makes the patient undesirable to participate in the study
  • 23\. Use of strong inducers of CYP3A4 within 14 days of half-lives (whichever is longer) prior to study day 1
  • 24\. Use of proton pump inhibitors within 14 days to study day

Key Trial Info

Start Date :

March 21 2022

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 31 2028

Estimated Enrollment :

19 Patients enrolled

Trial Details

Trial ID

NCT05398094

Start Date

March 21 2022

End Date

December 31 2028

Last Update

April 10 2025

Active Locations (20)

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Page 1 of 5 (20 locations)

1

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain, 08916

2

Hospitalario Universitario A Coruña

A Coruña, La Coruña, Spain, 15006

3

Hospital Universitario Severo Ochoa

Leganés, Madrid, Spain, 28911

4

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain, 28222